Long-term survival of encapsulated GDNF secreting cells implanted within the striatum of parkinsonized rats

Grandoso, Laura; Márquez, Sara Ponce; Manuel, Iván; Arrúe, Aurora; Ruiz-Ortega, José Ángel; Ulibarri, Isabel; Orive, Gorka; Hernández, R. M.; Rodríguez, Alicia; Rodrı́guez-Puertas, Rafael; Zumárraga, Mercedes; Linazasoro, Gurutz; Pedraz, José Luís; Ugedo, Luisa

doi:10.1016/j.ijpharm.2007.05.027

Cited by 63 publications

(21 citation statements)

References 36 publications

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“…So far measures available to enhance the survival of the grafted cells include neurotrophic support and antioxidant and antiopoptotic protection of the cells. Experimental evidences had shown that administration of such factors as GDNF, BDNF, and bFGF provided neurotrophic support of the grafted tissues or cells, and significantly enhanced the survival of the grafted neural stem cells or neurons in the host brain and improved the motor function of the animal models of PD [27][28][29]. Nakao et al [30] reported that lazaroids could obviously reduce the level of the free radicals to enhance the survival of the grafted dopaminergic neurons in a rodent model of PD.…”

Section: Discussionmentioning

confidence: 99%

Human Umbilical Vein-Derived Dopaminergic-Like Cell Transplantation with Nerve Growth Factor Ameliorates Motor Dysfunction in a Rat Model of Parkinson’s Disease

Zhang

Guo

et al. 2010

Neurochem Res

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Mesenchymal stem cells are capable of differentiating into dopaminergic-like cells, but currently no report has been available to describe the induction of human umbilical vein mesenchymal stem cells (HUVMSCs) into dopaminergic-like cells. In this study, we induced HUVMSCs in vitro into neurospheres constituted by neural stem-like cells, and further into cells bearing strong morphological, phenotypic and functional resemblances with dopaminergic-like cells. These HUVMSC-derived dopaminergic-like cells, after grafting into the brain of a rat model of Parkinson's disease (PD), showed a partial therapeutic effect in terms of the behavioral improvement. Nerve growth factor was reported to improve the local microenvironment of the grafted cells, and we therefore further tested the effect of dopaminergic-like cell grafting combined with nerve growth factor (NGF) administration at the site of cell transplantation. The results showed that NGF administration significantly promoted the survival of the grafted cells in the host brain and enhanced the content of dopaminergic in the local brain tissue. Behavioral test demonstrated a significant improvement of the motor function of the PD rats after dopaminergic-like cell grafting with NGF administration as compared with that of rats receiving the cell grafting only. These results suggest that transplantation of the dopaminergic-like cells combined with NGF administration may represent a new strategy of stem cell therapy for PD.

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Section: Discussionmentioning

confidence: 99%

Human Umbilical Vein-Derived Dopaminergic-Like Cell Transplantation with Nerve Growth Factor Ameliorates Motor Dysfunction in a Rat Model of Parkinson’s Disease

Zhang

Guo

et al. 2010

Neurochem Res

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“…This approach also presents some disadvantages such as the lack of control of the duration of the transgene expression, the viral spread outside the target area, and the difficulties in calculating the exact amount of GDNF produced from the viral-infected neurons. Finally, a different alternative would be the use of cell therapy strategies using cells genetically engineered to release GDNF [12]. However, several concerns have been raised, related to the reduced rate of cellular survival within the implanted graft, as well as the presence of immune rejection of the grafted cells by the host tissue.…”

Section: Introductionmentioning

confidence: 99%

Effective GDNF brain delivery using microspheres—A promising strategy for Parkinson's disease

Garbayo

Montero‐Menei

Ansorena

et al. 2009

Journal of Controlled Release

132

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Glial cell line-derived neurotrophic factor (GDNF) has shown promise in the treatment of neurodegenerative disorders of basal ganglia origin such us Parkinson's disease (PD). In this study, we investigated the neurorestorative effect of controlled GDNF delivery using biodegradable microspheres in an animal model with partial dopaminergic lesion. Microspheres were loaded with N-glycosylated recombinant GDNF and prepared using the Total Recirculation One-Machine System (TROMS). GDNF-loaded microparticles were unilaterally injected into the rat striatum by stereotaxic surgery two weeks after a unilateral partial 6-OHDA nigrostriatal lesion. Animals were tested for amphetamineinduced rotational asymmetry at different times and were sacrificed two months after microsphere implantation for immunohistochemical analysis. The putative presence of serum IgG antibodies against rat glycosylated GDNF was analyzed for addressing safety issues. The results demonstrated that GDNF-loaded microspheres, improved the rotational behavior induced by amphetamine of the GDNF-treated animals together with an increase in the density of TH positive fibers at the striatal level. The developed GDNF-loaded microparticles proved to be suitable to release biologically active GDNF over up to 5 weeks in vivo. Furthermore, none of the animals developed antibodies against GDNF demonstrating the safety of glycosylated GDNF use.

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“…4,5,28 Previous studies published by our group, as well as research conducted by numerous other laboratories, 16,29,30 has demonstrated that the administration of VEGF or GDNF improves behavioral deficits as well as decreases neuronal degeneration in different animal models of neurodegenerative disorders. 7,11,20 Nevertheless, the essential problems for the application of these hydrophilic molecules are their short half-life and rapid degradation rate in vivo. That is why many studies focus on designing different drug delivery systems to enhance the release of these proteins into the brain tissue, either through invasive or noninvasive methods.…”

Section: Discussionmentioning

confidence: 99%

“…GDNF is a potent factor that is able to act in vitro and in vivo, promoting the survival and differentiation of dopaminergic neurons and protecting these cells from dopaminergic toxins. [8][9][10][11][12] Several clinical trials have been conducted to analyze the potential of GDNF in PD patients; however, in all these studies, intracerebroventricularly or intraputaminally administered GDNF solution presented numerous negative side effects and no significant clinical improvements. [13][14][15] VEGF has prosurvival effects in neuronal culture and was demonstrated to be protective against 6-hydroxydopamine (6-OHDA) in a PD rat model.…”

mentioning

confidence: 99%

Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson’s disease

Herrán¹,

Requejo²,

Ruiz-Ortega³

et al. 2014

IJN

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Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson’s disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson’s disease.

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Long-term survival of encapsulated GDNF secreting cells implanted within the striatum of parkinsonized rats

Cited by 63 publications

References 36 publications

Human Umbilical Vein-Derived Dopaminergic-Like Cell Transplantation with Nerve Growth Factor Ameliorates Motor Dysfunction in a Rat Model of Parkinson’s Disease

Human Umbilical Vein-Derived Dopaminergic-Like Cell Transplantation with Nerve Growth Factor Ameliorates Motor Dysfunction in a Rat Model of Parkinson’s Disease

Effective GDNF brain delivery using microspheres—A promising strategy for Parkinson's disease

Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson’s disease

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Long-term survival of encapsulated GDNF secreting cells implanted within the striatum of parkinsonized rats

Cited by 63 publications

References 36 publications

Human Umbilical Vein-Derived Dopaminergic-Like Cell Transplantation with Nerve Growth Factor Ameliorates Motor Dysfunction in a Rat Model of Parkinson’s Disease

Human Umbilical Vein-Derived Dopaminergic-Like Cell Transplantation with Nerve Growth Factor Ameliorates Motor Dysfunction in a Rat Model of Parkinson’s Disease

Effective GDNF brain delivery using microspheres—A promising strategy for Parkinson's disease

Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson&rsquo;s disease

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Product

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Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson’s disease